Ink4c is dispensable for tumor suppression in Myc-induced B-cell lymphomagenesis

Abstract

p18 Ink4c functions as a dedicated inhibitor of cyclin-Ddependent kinases. Loss of Ink4c predisposes mice to tumor development and, in a dose-dependent manner, complements the tumor-promoting effects of various oncogenes. We have now addressed whether Ink4c loss impacts B-cell tumor development in the El-Myc transgenic mouse, a model of human Burkitt lymphoma. Loss of one or both alleles did not influence the onset of lymphoma in El-Myc transgenics, and did not appreciably affect Myc's proliferative or apoptotic responses in precancerous B cells. Nevertheless, Ink4c loss modulated the effects of Myc-induced transformation by decreasing the frequency of Arf loss, an ordinarily common event in El-Myc-induced lymphomas.

Selective ablation of the YxxM motif of IL-7Rα suppresses lymphomagenesis but maintains lymphocyte development

“…For example, nuclear factor-kB, the tumorsuppressor Ink4c, the death protein Apaf1/caspase9, as well as the DNA-modifying enzymes AID and Rag have all been shown to be dispensable for c-Myc-driven tumorigenesis (Scott et al, 2004;Keller et al, 2005;Kotani et al, 2007;Nilsson et al, 2007;Nepal et al, 2008). However, our data show that signals through IL7Ra Y449, such as STAT5, can regulate transformation in this lymphoma model.…”

Myc-induced SUMOylation is a therapeutic vulnerability for B-cell lymphoma

“…35 Given this, one is confronted with redundancy when trying to target individual genes or gene products. 7,[47][48][49] Nevertheless, Myc target genes with metabolic functions such as Odc 31 and ribosomal L24 21 are essential for Myc-driven lymphomagenesis. This raises the possibility that some metabolic or signaling nodes exist whose inhibition is synthetic lethal with Myc overexpression.…”